The Swiss heroin trials. Scientifically sound?

The objective of this article is to critique a study conducted by the Swiss Federal Office of Public Health to evaluate Switzerland's heroin maintenance project. Heroin abusers (N = 1,146) were enrolled in 18 research clinics. Subjects were recruited into three study arms--heroin, morphine, or methadone maintenance, but randomization was unsuccessful, and all received heroin. Medications were self-administered by injection on site. Patients were interviewed at intake and 6-month intervals up to 18 months. A review of the study revealed design weaknesses, including the absence of control groups, lack of corroboration of self-reports, failure to control for the influence of social services on outcome, and the absence of follow-up on those who left the trial prematurely. The program's ability to avert human immunodeficiency virus (HIV) transmission could not be fully evaluated because patients did not consistently submit to HIV testing. The Swiss trials of supervised heroin prescription trials do not withstand scientific scrutiny.

No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans.

BACKGROUND: Association studies between marker alleles at the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders; there has been a series of positive reports suggesting an association between DRD2 alleles and substance dependence in European-American (EA) subjects. METHODS: In an attempt to replicate the reported association between DRD2 alleles, substance dependence, and severity of substance dependence, we studied allele frequencies for three polymorphic DRD2 systems (TaqI "A," "B," and "D") in 96 EA and 77 African-American (AA) cocaine-dependent subjects, and 87 EA and 45 AA control subjects. To increase our power to detect such an association and to better understand any association detected, we also constructed three-locus haplotypes and compared haplotype frequencies. RESULTS: For both the EA and AA samples, there were no significant differences in allele frequency between substance-dependent and control subjects for any of the three DRD2 polymorphic systems studied. There were also no significant differences in haplotype frequency between substance-dependent and control subjects for either EA or AA subjects; and, finally, there were no significant differences in "A" or "B" system allele frequency by severity. There were, however, significant differences between EAs and AAs. CONCLUSIONS: Our data do not support an association between DRD2 alleles or haplotypes and cocaine dependence, in EA or AA subjects. Moreover, DRD2 alleles are not associated with severity of cocaine dependence in this sample.

Tryptophan depletion and attenuation of cue-induced craving for cocaine.

OBJECTIVE: Although cocaine is a potent serotonin (5-HT) reuptake blocker, the role of 5-HT systems in cocaine craving and relapse in humans has been unclear. The authors evaluated whether acute reductions in central 5-HT synthesis modulated craving for cocaine in cocaine-dependent patients. METHOD: Twenty-five cocaine-dependent male inpatients were exposed to cocaine-craving cues while their 5-HT levels were lowered and during a placebo condition in a counterbalanced, double-blind design. 5-HT levels were reduced by rapidly lowering plasma levels of its precursor, tryptophan; tryptophan levels were reduced by stimulating protein synthesis with a large drink of amino acids devoid of tryptophan. During the placebo condition the patients drank an identical amino acid drink containing tryptophan. Craving was induced by exposing patients to cocaine paraphernalia and a videotape depicting drug use. Craving was assessed 7 hours after ingestion of the drink. Visual analog ratings of craving for cocaine were administered before and after cue exposure at each test session. RESULTS: Patients reported less desire for cocaine stimulated by cue exposure after drinking amino acids without tryptophan than they did after drinking placebo. The order that tryptophan depletion and placebo tests were performed influenced the impact of tryptophan depletion on cue-induced craving. CONCLUSIONS: Serotonergic systems modulate cue-induced craving for cocaine, a factor implicated in relapse to cocaine use.

Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia.

Paranoia in the context of cocaine abuse is common and potentially dangerous. Several lines of evidence suggest that this phenomenon may be related to function of the dopamine transporter protein (DAT). DAT is the site of presynaptic reuptake of dopamine, an event that terminates its synaptic activity. The gene coding for dopamine transporter protein (DAT1) contains a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region that can be typed by the polymerase chain reaction (PCR) (Vandenbergh et al. 1992). Although this is not a coding region polymorphism, it is close to the coding region and could plausibly be in linkage disequilibrium with a mutation in the gene. Cocaine blocks the dopamine transporter and increases synaptic availability of dopamine. We examined DAT alleles in 58 white and 45 black cocaine users in order to test only two hypotheses: (1) Is there an allelic association between DAT and cocaine dependence? and (2) Is there an allelic association between DAT and cocaine-induced paranoia? We did not demonstrate an allelic association with cocaine dependence. However, within the white sample, DAT genotype was associated with cocaine-induced paranoia (allele frequency for allele 9 = .16 for those without paranoid experiences versus .35 for those with, chi 2 = 3.9 [2 x 2 table], p < .05). There was no significant difference for the same measure in the black sample. Certain DAT genotypes may therefore predispose to paranoia in the context of cocaine use in white populations. We caution that these results require independent replication.

Reducing obstacles to affiliation with alcoholics anonymous among veterans with PTSD and alcoholism.

Alcohol use is prevalent among Vietnam veterans who suffer from chronic combat-related posttraumatic stress disorder (PTSD). Although Alcoholics Anonymous (AA) is the mainstay of ambulatory alcoholism treatment, adherence to particular components of the AA philosophy may prove especially challenging for alcoholic Vietnam veterans with PTSD. The authors describe elements of AA's philosophy, such as "surrendering" to a "higher power," making amends to persons one has harmed, and sharing one's story publicly, that may be difficult for the Vietnam veteran with PTSD. The authors suggest that an important factor in the successful affiliation of these patients with AA is their capacity to separate their alcohol-related problems and treatment from their PTSD symptoms and treatment and to accommodate dual identities as both an alcoholic and a traumatized soldier. Preparing such patients for AA by reframing some of the 12 steps is recommended.

Language therapy for schizophrenic patients with persistent 'voices'.

One of us has hypothesised that the 'voices' of schizophrenic patients reflect altered preconscious planning of discourse that can produce involuntary 'inner speech' as well as incoherent overt speech. Some schizophrenic patients reporting voices do not, however, have disorganised speech. We hypothesise that these 'counterexample' patients compensate for impairments of discourse planning by reducing language complexity and relying on highly rehearsed topics. A 'language therapy' designed to challenge and enhance novel discourse planning was administered to four such patients; three had significant albeit temporary reductions in the severity of their voices. These clinical findings provide further evidence that alterations of discourse planning may underlie hallucinated voices.

Should protracted withdrawal from drugs be included in DSM-IV?

OBJECTIVE: The authors reviewed both clinical data and selected laboratory research related to withdrawal from alcohol, opiates, and stimulants in order to draw a conclusion about whether the phenomenon of protracted withdrawal exists and should be included in DSM-IV. METHOD: Studies were located through computerized searches and reference sections of published articles. RESULTS: Symptoms extending beyond the period of acute withdrawal in alcohol and opiate dependence have been fairly consistently described; this is not the case with cocaine. Nevertheless, protracted alcohol and opiate withdrawal has not been conclusively demonstrated because of the failure of studies to do multiple time point sampling, to use standardized instruments and control groups, and to re-administer the substance in an attempt to suppress withdrawal symptoms. Further, the concept of protracted withdrawal itself is ambiguously defined. This confounds interpretation of the literature and precludes derivation of a unified concept of the term, which would be necessary for adding the diagnosis to DSM-IV. CONCLUSIONS: There is insufficient documentation to justify inclusion of protracted withdrawal in DSM-IV because of methodologic limitations of the studies and lack of consensus definition of the term itself. An outline for conceptualizing protracted withdrawal is offered in which the symptoms can be seen as: 1) a global post-use syndrome, 2) attenuated physiologic rebound, 3) toxic residuals, 4) expression of preexisting symptoms unmasked by cessation of use. Future efforts to identify signs and symptoms of protracted withdrawal should carefully define the parameters of the syndrome.

Effects of cocaine on hospital course in schizophrenia.

The authors selected at random every fourth inpatient chart (N = 79) of patients enrolled in a schizophrenia clinic for analysis of substance use patterns and psychiatric hospitalizations. Patients were divided into three groups based on operationally defined lifetime drug use histories: a) cocaine and other substance use; b) substance use without cocaine; and c) no substance use. All available hospital records were examined for presenting symptoms and psychosocial functioning at admission, neuroleptic dosing, and hospital management. Cocaine-using schizophrenics had significantly higher hospitalization rates than other substance-using or non-using patients. No differences were found in hospital presenting symptoms among any cohort. However, the cocaine-using schizophrenic patients demonstrated significantly higher rates of suicidal ideation after cocaine use compared with their own non-cocaine-associated hospitalizations or the other groups. The cocaine group also received higher neuroleptic doses by the fifth and sixth weeks of hospitalization compared with their own non-cocaine-associated hospitalizations and with the other groups. This suggests that cocaine use in schizophrenia is associated with poorer illness course and increased hospitalization, including higher rates of suicidal ideation and greater neuroleptic dose.

Cocaine-induced paranoia and psychosis proneness.

OBJECTIVE: The aim of this study was to determine whether individuals who experience transient cocaine-induced paranoia are vulnerable to psychosis. METHOD: The subjects were 20 cocaine-dependent men who had been using more than 5 g of cocaine per week and were undergoing substance abuse treatment; half reported binge-limited cocaine-induced paranoia. The men were assessed with the Perceptual Aberration Scale and the Magical Ideation Scale, self-report measures of symptoms thought to precede the development of functional psychosis. RESULTS: The combined scores on the Perceptual Aberration Scale and Magical Ideation Scale were strongly correlated with a history of cocaine-induced paranoia. The sensitivity, specificity, and positive and negative predictive power were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. CONCLUSIONS: Heavy cocaine users who experience transient paranoia while intoxicated may be at higher risk for development of psychosis than cocaine users who do not experience paranoia.

Clinical phenomenology and neurobiology of cocaine abstinence: a prospective inpatient study.

OBJECTIVE: This study was undertaken to document symptoms and changes in dopaminergic function emerging after abrupt cessation of cocaine use. METHOD: After admission, 22 patients with DSM-III-R cocaine dependence were observed drug free for 3 weeks. The patient-rated Ribicoff Abstinence Rating Scale, Symptom Rating Scale, Physical Symptom Scale, Patient Rated Anxiety Scale, Beck Depression Inventory, and visual analogue scales for 16 subjective states were completed daily, and nurses rated 13 patients with the global anxiety and depression items of the Short Clinical Rating Scale. Serial blood samples were obtained three times weekly, and the patients' levels of prolactin, growth hormone (GH), and homovanillic acid (HVA) were measured. Their prolactin and GH values were compared with those of matched normal subjects. RESULTS: A total of 62 subjective symptom variables were evaluated. At baseline, the symptom ratings were mildly elevated. At 3 weeks there were significant decreases from baseline in 28 variables and nearly significant decreases in six additional variables. Nurse-rated anxiety and depression also changed, but in a more variable pattern. There was a small but significant increase from baseline over time in plasma prolactin, but there were no significant changes in GH or HVA. The patients' prolactin and GH values did not differ from those of the normal subjects. CONCLUSIONS: These findings suggest that symptoms after inpatient cessation of uncomplicated cocaine addiction are relatively mild and decrease linearly over the first month. Evidence of dysregulated central dopamine function was limited. The findings do not support routine use of pharmacological agents in the inpatient management of such patients.